Mammary cancer is the second most common tumor worldwide. Small animal mammary neoplasms provide an outstanding model to study cancer in humans, as tumors in both share a similar environment, histopathologic features, and biological behavior. This study aims to investigate the percentage and microscopy of breast tumors in affected dogs and cats; its relationship to breed, age, and sex; and the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), Ki-67, and cytokeratin 8. Twenty-four females (12 dogs and 12 cats) and one male were examined from February 2018 to February 2020. The highest percentage of mammary neoplasia from the highest to the lowest manifested as tubular carcinoma, leiomyosarcoma, fibroadenoma, and cystic papillary carcinoma. The current study reported the second micropapillary invasive carcinoma in a male cat and the third lipid-rich carcinoma in a female cat. Although tubular carcinoma was the most common mammary neoplasm in cats, leiomyosarcoma was the most common in dogs. The immunohistochemical staining revealed diffuse and intense cytoplasmic immunoreactivity for cytokeratin 8 in lipid-rich carcinomas. However, moderate expression of ER in benign tumors and slight to moderate ER expression in malignant mammary lesions were reported. On the contrary, there was a negative PR expression in benign lesion. It could be concluded that a close relationship between ER expression and nuclear antigen Ki-67 was found.

Studies have reported a sex bias in case fatalities of COVID-19 patients. Moreover, it is observed that men have a higher risk of developing a severe form of the disease compared to women, highlighting the importance of disaggregated data of male and female COVID-19 patients. On the other hand, other factors (eg, hormonal levels and immune functions) also need to be addressed due to the effects of sex differences on the outcomes of COVID-19 patients. An insight into the underlying causes of sex differences in COVID-19 patients may provide an opportunity for better care of the patients or prevention of the disease. The current study reviews the reports concerning with the sex differences in COVID-19 patients. It is explained how sex can affect angiotensin converting enzyme-2 (ACE2), that is a key component for the pathogenesis of COVID-19, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes. Furthermore, the available data about the impact of sex hormones on the immune functions of COVID-19 cases are looked into.

Excessive adipose accumulation, which is the main driver for the development of secondary metabolic complications, has reached epidemic proportions and combined pharmaceutical, educational and nutritional approaches are required to reverse the current rise in global obesity prevalence rates. Brown adipose tissue (BAT) is a unique organ able to dissipate energy and thus a promising target to enhance BMR to counteract a positive energy balance. In addition, active BAT might support body weight maintenance after weight loss to prevent/reduce relapse. Natural products deliver valuable bioactive compounds that have historically helped to alleviate disease symptoms. Interest in recent years has focused on identifying nutritional constituents that are able to induce BAT activity and thereby enhance energy expenditure. This review provides a summary of selected dietary phytochemicals, including isoflavones, catechins, stilbenes, the flavonoids quercetin, luteolin and resveratrol as well as the alkaloids berberine and capsaicin. Most of the discussed phytochemicals act through distinct molecular pathways e.g. sympathetic nerve activation, AMP-kinase signalling, SIRT1 activity or stimulation of oestrogen receptors. Thus, it might be possible to utilise this multitude of pathways to co-activate BAT using a fine-tuned combination of foods or combined nutritional supplements.

The objective of the present study was to investigate the effect of Gram-negative bacteria infection on ovarian steroid receptors, i.e. progesterone receptor (PR) and estradiol receptor (ER) during preimplantation days of pregnancy. A well established mouse model of Gram-negative bacteria infection was used to test this objective. Mice were treated with normal saline or lipopolysaccharide (LPS) on day 0.5 of pregnancy and used to collect embryos and uterine horns on day 1.5 to day 4.42 preimplantation day of pregnancy. Total RNA was extracted and reverse-transcription polymerase chain reaction (PCR) was performed to check the expression of PR and ER genes. The mRNA expression of PR and ER was altered in embryos and uterus of LPS-treated animals during preimplantation days of pregnancy studied. These results suggest that PR and ER play an important role in Gram-negative bacteria infection and induced implantation failure in mouse.

Background: Alzheimer's disease (AD) is a neurodegenerative disease with a higher prevalence in women. Expression of estrogen receptor 1 (ESR1) gene has been identified throughout the brain. Owing to the putative neuroprotective effects of estrogen, estrogen receptor gene is a potential candidate modulating the development of AD. Preliminary associations between two polymorphisms of ESR1 (PvuII and XbaI) gene and AD have been reported.

Methods: In this study, 16 single nucleotide polymorphisms (SNPs) of the ESR1 gene (including four commonly studied ESR1 SNPs and 12 other tagging SNPs selected from the HapMap database) were investigated to further evaluate the association between ESR1 polymorphisms and the risk of AD in the Chinese population.

Results: A total of 233 Chinese AD patients and 245 age-matched elderly control subjects were recruited. Genetic associations were analyzed by chi-square test and interaction effect was analysed by logistic regression analysis. Five SNPs (clustered between intron 3 and intron 7) were associated with the risk of AD (p-value ranges from 0.001 to 0.035); another two SNPs (located on exon 2 and intron 2) were shown to modulate the age-at-onset (AAO) in AD (p-value = 0.036 and 0.011).

Conclusions: ESR1 gene polymorphisms may be associated with the AAO in AD. The present results provided information for possible associations between certain polymorphisms of ESR1 gene and the risk of AD.

A plethora of in vitro and in vivo studies have supported the neuroprotective role of estrogens and their impact on the neurotransmitter systems implicated in cognition. Recent hormonal replacement therapy (HRT) trials in non-demented postmenopausal women suggest a temporary positive effect (notably on verbal memory), and four meta-analyses converge to suggest a possible protective effect in relation to Alzheimer's disease (reducing risk by 29 to 44%). However, data from the only large randomized controlled trial published to date, the Women's Health Initiative Memory Study, did not confirm these observations and have even suggested an increase in dementia risk for women using HRT compared to controls. Apart from methodological differences, one key shortcoming of this trial has probably been the focus on late-onset (postmenopausal) hormonal changes, i.e. at a time when the neurodegenerative process has already begun and without taking into account individual lifetime exposure to hormone variability. Multifactorial models based on an exhaustive view of all hormonal events throughout the reproductive life (rather than on a specific exposure to a given steroid) together with other risk factors (notably genetic risk factors related to estrogen receptor polymorphisms) should be explored to clarify the role of hormonal risk factors, or protective factors for cognitive dysfunction and dementia.

Tamoxifen can be considered a classic ‘pro-drug’, requiring metabolic activation to elicit pharmacological activity. Our findings suggest that both genetic and drug-induced factors that alter CYP2D6 enzyme activity influence the clinical response to tamoxifen. Given the small differences in disease-free survival comparing tamoxifen to third-generation aromatase inhibitors, knowledge of the genetic and environmental factors that influence CYP2D6 enzyme activity may provide a robust tool to individualize the hormonal therapy to breast cancer.

Histone acetylation is thought to facilitate binding of transcription factors (TFs) to specific target DNA sequences by destabilizing nucleosomes bound to the promoter region of a target gene. In addition, non-histone proteins including a subset of TFs and co-activators are acetylated by p300/CBP and P/CAF. The regulation of estrogen signaling by direct estrogen receptor alpha (ERα) post-translational modification reveals a novel role for histone acetyltransferase in hormone signaling. ERα is acetylated and phosphorylated and phosphorylation occurs at multiple sites in response to kinase signaling. The finding that mutations with the ERα hinge domain lysine residues enhance hormone sensitivity suggests these residues may be involved in ligand-dependent transcriptional repression or transcriptional attenuation. Phosphorylation and acetylation of the ER regulates hormone signaling and is being assessed for a role in resistance to anti-estrogen therapy of ERα-positive patients.

The estrogen receptor-alpha (ER-α) is a Type I nuclear receptor that is over-expressed in the majority of human breast cancers and plays a significant role in the development and progression of these cancers. As estrogen plays important roles in the etiology of breast cancer and the growth of established ER-α expressing cancers, intense interest has been generated in understanding the mechanisms by which ER-α signaling is regulated physiologically and using this knowledge to develop interventions to inhibit ER-α signaling. These efforts have met with some success in the development of pharmacologic agents that can reduce breast cancer risk, prevent recurrence of established cancers, and treat advanced cancers with considerably less side effects than cytotoxic chemotherapy. Here, we will review some of the mechanisms that operate to inhibit ER-α signaling and describe how pharmacologic agents and dietary factors interact with ER-α to block its activity. In the process of reviewing these mechanisms, we will highlight their clinical implications.

There is increasing evidence that 17β-estradiol is necessary for normal male fertility. The aim of the present study was to characterize estrogen receptor β (ERβ) expression in a non-mammalian vertebrate model, the lizard (Podarcis s. sicula) testis. Immunocytochemical analysis shows that ERβ proteins are present among germ cells in the nucleus of the spermatogonia, in primary spermatocytes and spermatids. Western blot analysis with antibodies against the ERβ gene product revealed an isoform with a specific weight of 55 kDa. In conclusion, the widespread expression of ERβ in the Podarcis s. sicula testis is consistent with a role for estrogens in modulating spermatogenesis in the male.